Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies

Ingemar S J Merkies; Ivo N van Schaik; Jean-Marc Léger; Vera Bril; Nan van Geloven; Hans-Peter Hartung; Richard A Lewis; Gen Sobue; John-Philip Lawo; Billie L Durn; David R Cornblath; Jan L De Bleecker; Claudia Sommer; Wim Robberecht; Mika Saarela; Jerzy Kamienowski; Zbigniew Stelmasiak; Björn Tackenberg; Orell Mielke; PRIMA Trial Investigators and the PATH Study Group

doi:10.1111/jns.12302

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies

J Peripher Nerv Syst. 2019 Mar;24(1):48-55. doi: 10.1111/jns.12302. Epub 2019 Feb 15.

Authors

Ingemar S J Merkies^{1

2}, Ivo N van Schaik³, Jean-Marc Léger⁴, Vera Bril^{5

6}, Nan van Geloven⁷, Hans-Peter Hartung⁸, Richard A Lewis⁹, Gen Sobue¹⁰, John-Philip Lawo¹¹, Billie L Durn¹¹, David R Cornblath¹², Jan L De Bleecker¹³, Claudia Sommer¹⁴, Wim Robberecht¹⁵, Mika Saarela¹⁶, Jerzy Kamienowski¹⁷, Zbigniew Stelmasiak¹⁸, Björn Tackenberg¹⁹, Orell Mielke¹¹; PRIMA Trial Investigators and the PATH Study Group

Collaborators

PRIMA Trial Investigators and the PATH Study Group:
A Sabet, K George, L Roberts, R Carne, S Blum, R Henderson, P Van Damme, J Demeestere, S Larue, C D'Amour, P Kunc, M Valis, J Sussova, T Kalous, R Talab, M Bednar, T Toomsoo, I Rubanovits, K Gross-Paju, U Sorro, M Saarela, M Auranen, J Pouget, S Attarian, G Le Masson, A Wielanek-Bachelet, C Desnuelle, E Delmont, P Clavelou, D Aufauvre, J Schmidt, J Zschuentzsch, C Sommer, D Kramer, O Hoffmann, C Goerlitz, J Haas, M Chatzopoulos, R Yoon, R Gold, P Berlit, A Jaspert-Grehl, D Liebetanz, A Kutschenko, M Stangel, C Trebst, P Baum, F Bergh, J Klehmet, A Meisel, F Klostermann, J Oechtering, H Lehmann, M Schroeter, T Hagenacker, D Mueller, A Sperfeld, F Bethke, V Drory, A Algom, D Yarnitsky, B Murinson, A Di Muzio, F Ciccocioppo, S Sorbi, S Mata, A Schenone, M Grandis, G Lauria, D Cazzato, G Antonini, S Morino, D Cocito, M Zibetti, T Yokota, T Ohkubo, T Kanda, M Kawai, K Kaida, H Onoue, S Kuwabara, M Mori, M Iijima, K Ohyama, M Baba, M Tomiyama, K Nishiyama, T Akutsu, K Yokoyama, K Kanai, I N van Schaik, F Eftimov, N C Notermans, N Visser, C Faber, J Hoeijmakers, K Rejdak, U Chyrchel-Paszkiewicz, C Casanovas Pons, M Antonia, J Gamez, M Salvado, C Marquez Infante, S Benitez, M Lunn, J Morrow, D Gosal, T Lavin, I Melamed, A Testori, S Ajroud-Driss, D Menichella, E Simpson, E Chi-Ho Lai, M Dimachkie, R J Barohn, S Beydoun, H Johl, D Lange, A Shtilbans, S Muley, S Ladha, M Freimer, J Kissel, N Latov, R Chin, E Ubogu, S Mumfrey, T Rao, P MacDonald, K Sharma, G Gonzalez, J Allen, D Walk, L Hobson-Webb, K Gable, J L De Bleecker, W Robberecht, M Saarela, J Franques, J-M Léger, R Juntas Morales, C Sommer, A Nguento, J Schmidt, Ch Schrey, J Kamienowski, Z Stelmasiak, G Zwolińska

Affiliations

¹ Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
² Department of Neurology, St Elisabeth Hospital, Willemstad, Curaçao.
³ Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
⁴ National Referral Center for Rare Neuromuscular Diseases, Hôpital Pitié-Salpêtrière and University Paris VI, Paris, France.
⁵ Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada.
⁶ Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
⁷ Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
⁸ Department of Neurology, UKD and Center for Neurology and Neuropsychiatry, LVR Klinikum, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
⁹ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California.
¹⁰ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹¹ CSL Behring, Marburg, Germany, and King of Prussia, Pennsylvania.
¹² Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹³ Department of Neurology, AZ St-Lucas, Ghent, Belgium.
¹⁴ Department of Neurology, Universitätsklinikum Würzburg, Würzburg, Germany.
¹⁵ Department of Neurosciences, UZ Leuven, Leuven, Belgium.
¹⁶ Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
¹⁷ Dolnośląski Szpital Specjalistyczny, Wrocław, Poland.
¹⁸ Department of Neurology, Samodzielny Publiczny Szpital Kliniczny, Lublin, Poland.
¹⁹ Department of Neurology, Philipps University, Marburg, Germany.

Abstract

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open-label, single-arm study of IVIG in immunoglobulin (Ig)-naïve or IVIG pre-treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double-blind, randomized study including an open-label, single-arm IVIG phase in IVIG pre-treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre-treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was -1.0 (interquartile range -2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA-approved IVIG for CIDP, in a population of mainly pre-treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].

Keywords: CIDP; IVIG; PATH; PRIMA; efficacy.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Double-Blind Method
Europe
Female
Humans
Immunoglobulins, Intravenous / administration & dosage
Immunoglobulins, Intravenous / pharmacology*
Immunologic Factors / administration & dosage
Immunologic Factors / pharmacology*
Male
Middle Aged
Outcome Assessment, Health Care*
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / drug therapy*
Prospective Studies
Young Adult

Substances

Immunoglobulins, Intravenous
Immunologic Factors